Esters of D-mannose or of xylitol and their use as medicaments

ABSTRACT

Esters associating phenylacetic, 3-phenylpropionic, 4-phenylbutyric and n-butyric acids with Su(OH) n  monosaccharides or sugar alcohols, of general formula (I), in which the Su(OH) n  precursor is a monosaccharide or sugar alcohol, selected so that its structure or that of its derivatives ensures that internal interesterification does not take place either because the ester based on the general formula does not have a free hydroxyl grouping, or because with regard to the ester grouping, the free hydroxyl groupings are remotely located and/or badly aligned and/or bonded to a secondary carbon atom, and in which the Su(OH) n  monosaccharide or sugar alcohol is preferably D-mannose carrying the ester grouping on the anomeric carbon atom or else is a pentitol, for example, xylitol carrying the ester grouping on the C-1 primary carbon atom. These novel esters are useful as drugs, in particular in the treatment of haemoglobin diseases and premalignant or malignant tumours.

The application is a 371 of PCT/FR95/00743, which was filed Jun. 7,1995.

The present invention relates to esters combining phenylacetic,3-phenylpropionic, 4-phenylbutyric and n-butyric acids with D-mannose,with xylitol and with their derivatives, and to their applications asmedicaments.

It is known that phenylacetic, 4-phenylbutyric and n-butyric acids andtheir salts stimulate the synthesis of foetal haemoglobin, in particularthat of the γ chain (E. Fibach et al., Blood (1993),82 (7), 2203; S. P.Perrine et al., Biochem. Biophys. Res. Comm. (1987), 148, 694).Moreover, they induce the γ gene of human foetal haemoglobin (J. W.Zhang et al., Developmental Genetics (1990), 11, 168; J. G. Glauber etal., Molec. Cell Biol. (1991), 11, 4690). These properties have beenturned to good account in the treatment of patients affected by anaemiaand by β-thalassaemic syndromes (S. P. Perrine et al., N. Engl. J. Med.(1993), 328, (2), 81).

It is also known that these acids and their salts inhibit the growth andinduce the differentiation of premalignant and malignant cells (D. Samidet al., Cancer Res. (1992), 52, 1988; E. Ginsburg et al., Proc. Natl.Acad. Sci. (1973), 70, 2457; K. Yamada et al., J. Cell. Physiol. (1985),125, 235; K. N. Prasad, Life Sciences (1980), 27, 1351), in particularof leukaemic cells (S. Fisckhoff et al., Leukemia (1990), 4, 302; D.Samid et al., Cancer Res. (1992), 52, 1988).

It is also known that n-butyric acid and its salts have a very short invivo plasma lifetime (P. Daniel et al., Clin. Chim. Acta (1989), 81,255). It is also known that esters resulting from the combination, via acovalent bond, of this acid with D-glucose, with D-galactose, withglycerol and with their derivatives are capable, in vivo, under theeffect of the enzymatic systems in man or in animals, of slowlyreleasing n-butyric acid with, as a result, a much longer plasmalifetime, thus providing a better bioavailability of the biologicallyactive part (F. Pieri et al., Patent FR 871294 (1987); Patent FR 8809092(1988); PCT 88004470 (1988); U.S. Pat. No. 071501 (1990)).

It is also known, from biological studies of the butyric estersmentioned above, that the best compound as a medicament is the monoester3-O-n-butanoyl-1,2-O-isopropylidene-α-D-glucofuranose (P. Pouillard,Thesus, Amiens, 1990; P. Planchon, Thesus, Amiens, 1991). However, thiscompound, as a result of its structure exhibiting 2 hydroxyl groups OHin the region of the O-n-butanoyl group, undergoes an internaltransesterification resulting, in solution, in the mixture of the 33-O-butanoyl, 5-O-butanoyl and 6-O-butanoyl isomers in proportions whichvary according to the operating conditions. Moreover, the isomerizationof this compound continues in a non-controllable way when the sample isdissolved, in particular in aqueous medium. This isomerization is inaccordance with the laws of chemistry, when, in a compound, a primaryhydroxyl group is sterically close to an ester group bonded to asecondary site and when this hydroxyl group has a steric orientationfavourable to the attack of the neighbouring acyl group (P. Y. Goueth etal., J. Carbohydr. Chem. (1994), 13 (2), 249). It is consequentlyimpossible to obtain this compound with a purity greater than 95%.

One of the aims of the present invention is to prepare esters combiningphenylacetic, 3-phenylpropionic, 4-phenylbutyric and n-butyric acidswith monosaccharides or itols (sugar-alcohols) Su(OH)_(n) selected sothat their structure or that of their derivatives prevents the internaltransesterification process responsible for the isomerization, whilemaking possible good bioavailability of the corresponding acid.

The aim is achieved according to the invention by the synthesis, forexample, of esters of general formula: ##STR1## in which themonosaccharide or itol (sugar-alcohols) Su(OH)_(n), the precursor of thecompounds in accordance with the invention, is preferably D-mannoseSu(OH)₅ ! carrying the ester group on the anomeric carbon atom oralternatively a pentitol Su(OH)₅ ! such as, for example, xylitolcarrying the ester group on the C-1 primary carbon atom;

in which R₁ --CO is the phenylacetyl, 3-phenylpropanoyl,4-phenylbutanoyl or n-butanoyl group;

in which R₂, R₃, R₄ and R₅ can be the hydrogen atom or groups containingor not containing a hydrocarbon chain, which are cyclic or non-cyclic,which are saturated or unsaturated and which are branched or unbranchedor alternatively selected so that R₂ and R₃ and/or R₄ and R₅ belong toan acetal group in the dioxolane form: ##STR2## with the R--C--R' grouppreferably selected from phenylmethylene, methylene, cyclohexylidene or,better, isopropylidene;

and in which the internal transesterification in solution is prevented,either because the compounds do not have a free hydroxyl group orbecause the compounds have, with respect to the ester group, freehydroxyl groups which are distant and/or poorly oriented and/or bondedto a secondary carbon atom.

When, for example, the preparation of the esters, in accordance with thepresent invention, is carried out from di-O-acetals of D-mannose or ofxylitol, the synthesis can take place, for example, according to Stagea, optionally followed by Stages b and/or c, as illustrated by Scheme 1for the D-mannose compounds of type A and B and by Scheme 2 for thexylitol compounds of type C. ##STR3##

Stage a: Synthesis of the α- andβ-O-acyl-2,3:5,6-di-O-acetal-D-mannoside (α-DAM-A and β-DAM-B) estersand of the 1-O-acyl-2,3:4,5-di-O-acetalxylitol (DAXyli-C) esters.

These esters can be prepared, for example, by addition of an acylatingagent R₁ --CO--Y to the diacetal DAMannose and DAXylitol respectively,the preparation optionally being carried out in a solvent and in thepresence of a base.

The acylating agent can be the acid (Y═OH), the acid anhydride(Y═O--CO--R₁), an ester (Y═OR", with R"═CH₃ or C₂ H₅) or better the acidchloride (Y═Cl).

The solvent can be polar or non-polar, aliphatic or aromatic, alone or amixture of these solvents.

The base can be a weak inorganic or organic base selected, for example,from an alkaline carbonate, pyridine or, better, triethylamine.

The acylation of the diacetal DAMannose results in the mixture ofα-DAM-A and β-DAM-B anomeric esters. These esters are separated, forexample, by liquid chromatography of the mixture.

Stage b: Preparation of the α- and β-O-acyl-2,3-O-acetal-D-mannoside(α-MAM-A and β-MAM-B) monoacetal esters and of the1-O-acyl-2,3-O-acetalxylitol (MAXyli-C) esters by selective deprotectionof the corresponding diacetal esters.

The selective deprotection of an acetal site according to Stage b ofSchemes 1 and 2 is carried out in a hydroxylated solvent SOH by acidcatalysis, either in homogeneous phase or in heterogeneous phase:

The hydroxylated solvent can be water, an alkanol, a water/alkanolmixture, an alkanol/alkanol mixture or alternatively water or alkanol incombination with a non-hydroxylated cosolvent. The alkanol can beselected, for example, from methanol, ethanol or propanol.

The cosolvent can be selected, for example, from dioxane ortetrahydrofuran.

The acid catalysis in homogeneous phase can be carried out by theaddition to the medium of organic or inorganic acids. The organic acidcan be selected from carboxylic or sulphonic acids, such as, forexample, formic, acetic, trifluoroacetic and para-toluenesulphonicacids. The inorganic acid can be selected, for example, from sulphuric,hydrochloric, nitric and phosphoric acids. The α-MAM-A, β-MAM-B andMAXyli-C esters are obtained, in the pure state, after neutralization ofthe medium with an organic or inorganic base, filtration, evaporation ofthe solvent and purification by liquid chromatography, for example.

The acid catalysis in heterogeneous phase can be carried out by thepresence, in the medium, of an acid resin or by percolation through acolumn filled with acid resin of the solution of ester in thehydroxylated solvent (SOH) defined above. The α-MAM-A, β-MAM-B andMAXyli-C esters are isolated in the pure state after filtration,evaporation of the solvent and purification by liquid chromatography,for example.

The D-mannose derivatives of α-MAM-A and β-MAM-B type, as well as thexylitol derivatives of MAXyli-C type, which, with respect to the estergroup, have free hydroxyl groups which are distant and/or poorlyoriented and/or bonded to a secondary carbon atom, cannot give rise, insolution, to an internal transesterification.

Stages c₁ and c₂ : Preparation of the α- and β-O-acyl-D-mannoside (α-M-Aand β-M-B) esters and of the 1-O-acylxylitol (Xyli-C) esters bydeprotection of the corresponding monoacetal or diacetal esters.

The deprotection of the diacetal ester according to Stage c₁ or of themonoacetal ester according to Stage c₂ of Schemes 1 and 2 can be carriedout with the same solvents (SOH) and with the same acids as thosedefined for Stage b of the present invention, the amount of acid, thetemperature and the duration of the reaction optionally being adjusted.

The D-mannose derivatives of α-M-A type and of β-M-B type, as well asthe xylitol derivatives of Xyli-C type, which, with respect to the estergroup, have free hydroxyl groups which are distant and/or poorlyoriented and/or bonded to a secondary carbon atom, cannot give rise, insolution, to an internal transesterification.

Another aim of the invention is the use, as medicaments, of the esterscombining phenylacetic, 3-phenylpropionic, 4-phenylbutyric and n-butyricacids with D-mannose, with xylitol and with their derivatives, ofgeneral formula: ##STR4##

The use is targeted in particular, as with the corresponding acids andsalts, and without being limiting, at haemoglobinopathies, such as, forexample, anaemias, β-thalassaemia or drepanocytosis, or alternativelypremalignant and malignant tumours, such as, for example, cancer of thebreast, cancer of the colon or acute and chronic leukaemias.

The esters described in the present invention are also distinguishedfrom the corresponding esters and salts by a much longer plasma life,which results in a much greater bioavailability, making it possible toenvisage long-term treatments in man.

A description is given below of the preparation of esters of D-mannose,of xylitol and of their derivatives, in accordance with the presentinvention, by way of examples and without this being regarded aslimiting.

EXAMPLE NO. 1 Preparation of the α- andβ-O-acyl-2,3:5,6-di-O-isopropylidene-D-mannofuranosides (α-DAM-A andβ-DAM-B)

a) Esterification of diacetonemannose with n-butanoyl chloride.

260 g (1 mol) of diacetonemannose(2,3:5,6-di-O-isopropylidene-D-mannose) are dissolved with stirring in a3 L reactor, thermostatically controlled at 60° C., containing 2.6 L oftoluene. The solution is brought to boiling point under reduced pressureat 60° C. in order to remove, by distillation, the possible traces ofwater in the form of a water/toluene azeotrope. After having recovered100 mL of distillate, monitoring by the Karl-Fischer method shows thatthe solution in the reactor is completely anhydrous. The medium is thenbrought back to atmospheric pressure and, at room temperature, 106 g(1.05 mol) of triethylamine (TEA) are run in, followed, dropwise andwith stirring, by 106.5 g (1 mol) of n-butanoyl chloride (duration ofthe addition: 10 minutes). Monitoring, carried out by VPC (OV17 column),shows the complete disappearance of the diacetonemannose after reactingfor 60 minutes.

The toluene solution is filtered in order to remove the TEAhydrochloride. The filtrate, evaporated under reduced pressure, gives332 g of crude syrupy product. The composition, determined by VPC (OV 17column), is 90% of α anomer and 10% of β anomer.

b) Separation of the α-DAM-B and β-DAM-B anomeric butyrates.

500 mL of acetone and 300 g of neutral 60 Å silica, 35-40 mesh, areadded to the 332 g of crude product above. This mixture is evaporatedunder reduced pressure. The sediment is transferred onto a column(diameter 40 mm) containing 700 g of silica. Elution is carried out witha hexane/acetone mixture with an increasing acetone gradient.

The following are successively isolated:

after passage of 10 L of the hexane/acetone (97/3, v/v) mixture, 290 gof pure a anomer, which is liquid at room temperature;

α!_(D) ²³ =+43.5° (c=1.1; CHCl₃);

the ¹ H and ¹³ C NMR spectra (Table 1) are in accordance with thestructure of the α anomer;

after passage of 1 L of the hexane/acetone (96/4, v/v) mixture, 1.5 g ofα,β mixture;

after passage of 4 L of the hexane/acetone (90/10, v/v) mixture, 28 g ofpure β anomer, which is liquid at room temperature;

α!_(D) ²⁰ =+23.2° (c=1.2; CHCl₃);

the ¹ H and ¹³ C NMR spectra (Table 2) are in accordance with thestructure of the β anomer.

The total mass of the esters recovered is 319.5 g, i.e. a yield of 97%with respect to the diacetonemannose. The final yield of purifiedanomeric diacetonemannose butyrates is thus 88% of α ester and 9% of βester.

c) Preparation of the α- andβ-O-acyl-2,3:5,6-di-O-isopropylidene-D-mannosides (α-DAM-A and β-DAM-B),with acyl=Ph--(CH₂)_(n) --O and n=1, 2 or 3.

These esters are prepared under the same conditions as the correspondingn-butyrates (cf. a) but with amounts which are ten times smaller. Theduration of the reaction, the α/β distribution of the anomers, thecomposition of the chromatography eluent for isolating the α-anomer, andthe yield and the physical constants of the latter are given in thetable below.

    __________________________________________________________________________              DAM-Aa.                                                               Duration                                                                              % Hex./Ac.                                                                          Yd isolated                                                                          a!.sub.D in CHCl.sub.3                                                               M.p.  NMR                                       n (h)  α/β                                                                   (v/v) (%)   (T°C.; c = %)                                                                  (°C.)                                                                        Table                                     __________________________________________________________________________    1 2.5  81/19                                                                            95/5  75    +18.2° (25; 1.6)                                                               79-82 3                                         2 2.5  83/17                                                                            95/5  75    +34.6° (26; 1.6)                                                               105.4-105.7                                                                         4                                         3 4.0  86/14                                                                            94/6  76    +33.3° (27; 1.1)                                                               liquid                                                                              5                                         __________________________________________________________________________

The ¹ H and ¹³ C NMR spectra are in accordance with the structure of theexpected products.

EXAMPLE NO. 2 Preparation of theα-O-acyl-2,3-O-isopropylidene-D-mannofuranosides (α-MAN-A)

a) Selective acid-catalysed deprotection of the α-DAM-A butyrate.

a.1) Experimental conditions and rate of deprotection on acid resins.

20 g of Amberlite 15H⁺ wet acid resin and 15 g of α ester are stirred in135 mL of 96^(c) ethanol in a round-bottomed flask thermostaticallycontrolled at 51° C. The kinetics, monitored by HPLC (RP 18 column)quantitative determination of samples taken at intervals, show that thedeprotection rate constant according to the pseudo-first-order law isk=1.10×10⁻² min⁻¹, which corresponds to a degree of progression of 93%after reacting for 4 hours. HPLC (RP 18 column) analysis of the sampletaken after 4 hours shows the presence of 2 signals of relativeintensities 93/7. The more intense corresponds to a more polar productidentified, by the analyses described hereinbelow in 2-b, as beingO-n-butanoyl-2,3-O-isopropylidene-α-D-mannoside.

Under these experimental conditions, there is highly selectivedeprotection of the 5,6-O-isopropylidene group.

a.2) Quantitative deprotection of the α-DAM-A butyrate on acid resins.

The procedure is as in a.1, with 2.25 L of 96^(c) ethanol, 187.5 g ofacid resin and 250 g of α-DAM-A ester. After reacting for 4 hours, themixture is filtered and the resins are rinsed with 2 times 200 mL of96^(c) ethanol. The evaporation of the combined alcoholic solutionsmakes it possible to recover 220 g of solid residue.

a.3) Selective acid-catalysed deprotection of the α-DAM-A butyrate inhomogeneous medium.

The deprotection of the ester was also carried out in homogeneoussolution in a round-bottomed flask, thermostatically controlled at 30°C., containing 100 mL of 96^(c) ethanol, or 100 mL of dioxane/water(80/20, v/v) solvent, with 0.2N H₂ SO₄ and 15 g of α-DAM-A butyrate.

The degree of deprotection exceeds 90% after reacting for 4 hours. Theextraction of the product involves neutralization by an aqueous sodiumhydroxide solution. To prevent deesterification of the product, additionof the base must be performed at low temperature (0° to 10° C.) andhalted as soon as the pH of the medium reaches 7 units. The crudeproduct is isolated after separation of the sodium sulphate byfiltration and evaporation of the solvent under reduced pressure.

b) Purification of the α-MAM-A butyrate.

500 mL of toluene and 250 g of neutral 60 Å silica, 35-40 mesh, areadded to the 220 g of solid residue above. This mixture is evaporatedunder reduced pressure. The sediment is transferred onto a column(diameter 40 mm) containing 750 g of silica. Elution is carried out witha hexane/acetone mixture with an increasing acetone gradient.

The following are successively isolated:

after passage of 4.5 L of hexane/acetone (85/15, v/v) mixture, 15 g ofα-DAM-A ester;

after passage of 6 L of hexane/acetone (70/30, v/v) mixture, 190 g ofO-n-butanoyl-2,3-O-isopropylidene-α-D-mannoside-α-MAM-A sic!;

α!_(D) ²² =+54.6° (c=1.2; CHCl₃);

M.p.=79° C.;

the ¹ H and ¹³ C NMR spectra (Table 6) are in accordance with thestructure of the expected product;

after passage of 1 L of the hexane/acetone (50/50, v/v) mixture and thenof 2 L of pure acetone, 6 g of mixture mostly containingO-n-butanoyl-α-D-mannoside and then 3 g of pureO-n-butanoyl-α-Dmannoside from HPLC analysis.

c) Preparations of the O-acyl-2,3-O-isopropylidene-α-D-mannofuranoside(α-MAM-A) esters, with acyl=Ph--(CH₂)_(n) --CO and n=1, 2 or 3.

These esters are prepared under the same conditions as the correspondingn-butyrates (cf. a.2) but with amounts which are ten times smaller. Theduration of the reaction, the composition of the chromatography eluent,the yield and the physical constants are given in the table below.

    __________________________________________________________________________       Duration                                                                           Hex./Ac.                                                                            Yd isolated                                                                          a!.sub.D in CHCl.sub.3                                                               M.p.  NMR                                         n  (h)  (v/v) (%)   (T°C.; c = %)                                                                  (°C.)                                                                        Table                                       __________________________________________________________________________    1  4.0  75/25 75    +32.2° (25; 1.6)                                                               liquid                                                                              7                                           2  4.5  70/30 77    +34.6° (26; 1.6)                                                               30.5-33.6                                                                           8                                           3  3.5  75/25 77    +33.3° (27; 1.1)                                                               70.2-72.6                                                                           9                                           __________________________________________________________________________

The ¹ H and ¹³ C NMR spectra are in accordance with the nature of theexpected products.

EXAMPLE NO. 3 Preparation of the1-O-acyl-2,3:4,5-di-O-isopropylidenexylitol (DAxyli -C)

a) Esterification of diacetonexylitol with n-butanoyl chloride.

100 g (0.43 mol) of diacetonexylitol(2,3:4,5-di-O-isopropylidenexylitol) are dissolved with stirring in a 3L reactor, thermostatically controlled at 60° C., containing 800 mL oftoluene. The solution is brought to boiling point under reduced pressureat 60° C. in order to remove, by distillation, the possible traces ofwater in the form of a water/toluene azeotrope. After having recovered40 mL of distillate, monitoring by the Karl-Fischer method shows thatthe solution in the reactor is completely anhydrous. The medium is thenbrought back to atmospheric pressure and, at room temperature, 47.1 g(0.47 mol) of triethylamine (TEA) are run in, followed, dropwise andwith stirring, by 45.9 g (0.43 mol) of butanoyl chloride (duration ofthe addition 7 minutes). Monitoring, carried out by VPC (OV17 column),shows the complete disappearance of the diacetonexylitol after reactingfor 4 hours.

The toluene solution is filtered in order to remove the TEAhydrochloride. The filtrate, evaporated under reduced pressure, gives131 g of crude syrupy product.

b) Purification of the DAXyli-C butyrate.

250 mL of acetone and 100 g of neutral 60 Å silica, 35-40 mesh, areadded to the 131 g of crude product above. This mixture is evaporatedunder reduced pressure. The sediment is transferred onto a column(diameter 40 mm) containing 400 g of silica. Elution is carried out witha hexane/acetone mixture with an increasing acetone gradient.

After passage of the hexane/acetone (98/2, v/v) mixture, 108.7 g of pureester are isolated, i.e. a yield of 84% with respect to thediacetonexylitol;

α!_(D) ²³ =-0.3° (c=1.7; CHCl₃);

the ¹ H and ¹³ C NMR spectra (Table 10) are in accordance with thestructure of the α anomer.

c) Preparation of the 1-O-acyl-2,3:4,5-di-O-isopropylidenexylitolesters, with acyl=Ph--(CH₂)_(n) --O and n=1, 2 or 3.

These esters are prepared are prepared under the same conditions as thecorresponding n-butyrates (cf. a) but with amounts which are ten timessmaller. These compounds are liquid at room temperature. The duration ofthe reaction, the composition of the chromatography eluent, the yieldsand the physical constants are given in the table below.

    ______________________________________                                             Duration Hex./Ac.  Yd isolated                                                                            α!.sub.D in CHCl.sub.3                                                           NMR                                 n    (h)      (v/v)     (%)     (T°C.; c = %)                                                                    Table                               ______________________________________                                        1    5.0      90/10     86      -1.6° (29; 1.0)                                                                  11                                  2    3.0      95/5      91      -1.1° (29; 1.0)                                                                  12                                  3    4.0      90/10     89      -1.7° (29; 1.1)                                                                  13                                  ______________________________________                                    

The ¹ H and 13 C NMR spectra are in accordance with the structure of theexpected products.

EXAMPLE NO. 4 Preparation of the 1-O-acyl-2,3-O-isopropylidenexylitol(MAXyli-C) and of the 1-O-acylxylitol (Xyli -C)

a) Selective and complete acid-catalysed deprotections of the DAXyli-Cbutyrate.

200 g of Amberlyst 15H⁺ wet acid resin and 100 g of ester are stirred in800 mL of 96^(c) ethanol in a round-bottomed flask thermostaticallycontrolled at 52° C. The kinetics, monitored by HPLC (RP 18 column)quantitative determination of samples taken at intervals, show thatthere is a degree of progression of 98% after reacting for 4 hours. HPLCanalysis of the sample taken shows the presence of 2 signals of relativeintensities 7/3. The more intense corresponds to a more polar productidentified, by the analyses described hereinbelow in 4-b, as being1-O-n-butanoylxylitol. After reacting for 4 hours, the mixture isfiltered and the resins are rinsed with 2 times 200 mL of 96^(c)ethanol. Evaporation of the combined alcoholic solutions makes itpossible to recover 79 g of syrupy liquid.

b) Separation of the MAXyli-C and Xyli-C butyrates.

150 mL of ₉₆ c ethanol and 80 g of neutral 60 Å0 silica, 35-40 mesh, areadded to the 79 g of crude product above. This mixture is evaporatedunder reduced pressure. The sediment is transferred onto a column(diameter 30 mm) containing 320 g of silica. Elution is carried out withan industrial hexane/acetone mixture with an increasing acetonegradient.

The following are successively isolated:

after passage of 7 L of the hexane/acetone (75/25, v/v) mixture, 25 g ofpure MAXyli-C ester, which is liquid at room temperature;

α!_(D) ²⁶ =+0.3° (c=1.2; CHCl₃);

the ¹ H and ¹³ C NMR spectra (Table 14) are in accordance with thestructure of the expected product;

after passage of the hexane/acetone (20/80, v/v) mixture, 46.8 g of pureXyli-C ester, which is liquid at room temperature;

α!_(D) ²⁶ =+1.3° (1.1; CHCl₃);

the ¹ H and ¹³ C NMR spectra (Table 15) are in accordance with thestructure of the expected product.

c) Preparation of the 1-O-acyl-2,3-O-isopropylidenexylitol (MAXyli-C)and 1-O-acylxylitol (Xyli-C) esters, with acyl=Ph--(CH₂)_(n) --O andn=1, 2 or 3.

These esters are prepared under the same conditions as the correspondingn-butyrates (cf. a) but with amounts which are ten times smaller. Theduration of the reaction, the distribution of the MAXyli-C and Xyli-Cesters, the composition of the eluent in order to isolate each of them,and the yield and the physical constants of these compounds are given inthe table below.

    ______________________________________                                                                 Yd                                                       Dur-            Hex./                                                                              iso-                                                     ation           Ac.  lated                                                                               α!.sub.D in MeOH                                                                M.p.   NMR                             n   (h)    Product  (v/v)                                                                              (%)  (T° C.; c = %)                                                                  (°C.)                                                                         Table                           ______________________________________                                        1   2.5    MAXyli-C 88/22                                                                              32   -4.1° (30; 1.2)                                                                 liquid 16                                         Xyli-C   40/60                                                                              56   -2.0° (30; 1.0)                                                                 66.8-69.3                                                                            17                              2   3.0    MAXyli-C 75/25                                                                              36   -5.5° (31; 1.0)                                                                 liquid 18                                         Xyli-C   35/65                                                                              60   -1.7° (30; 1.1)                                                                 liquid 19                              3   2.5    MAXyli-C 75/25                                                                              36   -3.2° (31; 1.8)                                                                 liquid 20                                         Xyli-C   25/75                                                                              62   -3.0° (30; 1.0)                                                                 39.5-42.8                                                                            21                              ______________________________________                                    

The ¹ H and ¹³ C NMR spectra are in accordance with the structure of theexpected products.

EXAMPLE NO. 5 Chemical stability of the esters in aqueous medium

The α-O-acyl-2,3-O-isopropylidenemannoside esters described in ExampleNo. 2, as well as the 1-O-acyl-2,3-O-isopropylidenexylitol and1-O-acylxylitol esters described in Example No. 4, were subjected toprolonged monitoring of stability in solution under the conditionsbelow:

1. in distilled water (pH=6.5) at 4° C. and at 25° C.;

2. in a 50/50 (v/v) water/ethanol mixture at 25° C.;

3. in distilled water with 0.2 mol.L⁻¹ CO₃ HNa (pH=8.1) at 25° C.

Results

Under the conditions 1. and 2., monitoring carried out by HPLC (RP 18column, water/acetone eluent) shows that the loss of ester by hydrolysisis less than 1% after one month in solution. In addition, evaporationafter one month, followed by liquid chromatography, makes it possible torecover the pure ester, from its physical and spectroscopic constants,the mass of which represents 98% of the mass of the ester initiallydissolved.

Under the conditions 3., monitoring operations carried out by HPLC, asfor 1. and 2., show a faster deesterification of the esters than underthe above conditions, because of the basicity of the medium (pH=8.1,against 6.5 under the conditions 1.). This deesterification takes placeat a rate in the region of that observed for3-O-n-butanoyl-1,2-O-isopropylidene-α-D-glucofuranose under the sameconditions (Goueth et al., J. Carbohydr. Chem. (1994), 13 (2), 249),i.e. 20% in 95 hours, against 15 to 25% for the esters studied. However,for each of the esters described here, the ester fraction recoveredafter 95 hours has the same physical and spectroscopic constants as theproduct initially dissolved, whereas, for3-O-n-butanoyl-1,2-O-iso-propylidene-α-D-glucofuranose, thenon-deesterified fraction is composed of 6% of the initial ester, 90% ofthe 6-O-n-butanoyl isomer and 4% of the 5-O-n-butanoyl isomer.

EXAMPLE NO. 6 Demonstration of the antiproliferative and cell maturationproperties of the α-MAM-A, MAXyli-C and Xyli-C butyric esters (R₁ =n-C₃H₇) on lines responsible for acute myeloid leukaemia

The tests were carried out on stabilized cell lines (HL 60 and others)in the absence of growth factors. The concentrations of butyricderivatives vary from 0.5 to 1 mM.

The following parameters were evaluated by "FASC Scan" scanning and flowcytometry:

incorporation of tritiated thymidine (exploration of cell metabolism);

incorporation of propylium iodide (determination of the phase of thecell cycle);

evaluation of the level of cells in the apoptosis phase (programmed celldeath);

evaluation of cell maturation (quantitative determination of the surfaceantigens by specific monoclonal antibodies).

The antiproliferative properties are demonstrated by the data in thetable below on the percentage of inhibition of cell growth and on thepercentage of cells in apoptosis.

    ______________________________________                                        Butyric compounds                                                                        % of inhibition of                                                                          % of apoptosis                                       (R.sub.1 = n-C.sub.3 H.sub.7)                                                            growth HL 60 (n days)                                                                       HL 60 and others (3 days)                            ______________________________________                                        α-MAM-A                                                                            40 (2 d.)     13 to 84, depending                                             80 (5 d.)     on the line                                          MAXyli-C   80 (3 d.)     27 to 96, depending                                             90 (4 d.)     on the line                                          Xyli-C     70 (5 d.)     10 to 35, depending                                                           on the line                                          ______________________________________                                    

The maturation of the myeloid cells is evaluated by the expression ofthe specific antigens CD 15, CD 11a and CD 11b. The three aboveproducts, at a concentration of 1 mM, cause only a marginal increase inthe specific antigens for maturation.

EXAMPLE NO. 7 Demonstration of the effect of the α-MAC-A and Xyli-Cbutyric esters (R₁ =n-C₃ H₇) on the synthesis of foetal haemoglobin

The tests were carried out on erythroleukaemic cell lines in thepresence of normal human serum.

The following parameters were evaluated:

level of γ chain of the haemoglobin (immunological quantitativedetermination by double antigen antibody reaction and byimmunocytochemical quantitative determination in the presence ofalkaline phosphatase-anti-alkaline phosphatase A.P.A.A.P.);

level of mRNA of the γ chains (Northern Blot Analysis).

It is observed that the α-MAM-A and Xyli-C esters, at the respectiveconcentrations of 0.70 mM and 0.35 mM, increase the level of γ chain ofthe haemoglobin.

In the presence of A.P.A.A.P., this level changes from 10% without esterto 22% with α-MAM-A and to 17% with Xyli-C. The test for detection ofthe mRNAs of the γ chains in the presence of the above esters shows in avery significant way the increase in the mRNAs.

                  TABLE 1                                                         ______________________________________                                        .sup.1 H and .sup.13 C NMR spectra of O-n-butanoyl-2,3:5,6-di-O-isopropyli    dene-                                                                         α-D-mannoside.                                                           ##STR5##                                                                     C      δ (ppm)                                                                           H        δ (ppm)                                                                          J (Hz)                                     ______________________________________                                        C.sub.1                                                                              99.4      H.sub.1  5.94  s    J.sub.1-2 = 0                            C.sub.2                                                                              83.9      H.sub.2  4.50  d    J.sub.2-3 = 5.8                          C.sub.3                                                                              78.2      H.sub.3  4.67  dd   J.sub.3-4 = 3.7                          C.sub.4                                                                              81.1      H.sub.4  3.82  m    J.sub.4-5 = 4.4                          C.sub.5                                                                              71.8      H.sub.5  4.20  m    J.sub.5-6a = 6.2                         C.sub.6                                                                              65.7      H.sub.6a 3.90  dd   J.sub.6a-6b = 8.7                        C.sub.iso                                                                            112.0     H.sub.6b 3.82  m    J.sub.5-6b = 7.6                         C.sub.iso                                                                            108.1     CH.sub.3 iso                                                                           1.29  s    --                                       CH.sub.3                                                                             25.8      CH.sub.3 iso                                                                           1.26  s    --                                       CH.sub.3                                                                             24.8      CH.sub.3 iso                                                                           1.18  s    --                                       CH.sub.3                                                                             24.0      CH.sub.3 iso                                                                           1.15  s    --                                       CH.sub.3                                                                             23.5      H.sub.2 '                                                                              2.10  t    J.sub.2'-3'  = 7.2                       C.sub.1'                                                                             170.7     H.sub.3' 1.46  q    J.sub.3'-4'  = 7.4                       C.sub.2'                                                                             34.9      H.sub.4' 0.76  t    --                                       C.sub.3'                                                                             17.1                                                                   C.sub.4'                                                                             12.4                                                                   ______________________________________                                         (Solvent: CDCl.sub.3 ; chemical shift δ with respect to the TMS         signal).                                                                 

                  TABLE 2                                                         ______________________________________                                        .sup.1 H and .sup.13 C NMR spectra of O-n-butanoyl-2,3:5,6-di-O-isopropyli    dene-                                                                         β-D-mannoside.                                                            ##STR6##                                                                     C      δ (ppm)                                                                           H        δ (ppm)                                                                           J (Hz)                                    ______________________________________                                        C.sub.1                                                                              95.4      H.sub.1  5.66  d     J.sub.1-2 = 2.9                         C.sub.2                                                                              77.8      H.sub.2  4.63  m     J.sub.2-3 = n.d.                        C.sub.3                                                                              78.4      H.sub.3  4.63  m     J.sub.3-4 = 2.8                         C.sub.4                                                                              77.4      H.sub.4  3.62  dd    J.sub.4-5 = 7.8                         C.sub.5                                                                              72.1      H.sub.5  4.24  m     J.sub.5-6a = n.d.                       C.sub.6                                                                              65.7      H.sub.6a 3.87        J.sub.6a-6b = n.d.                      C.sub.iso                                                                            113.2     H.sub.6b AA'X  Syst. J.sub.5-6b = n.d.                       C.sub.iso                                                                            108.3     CH.sub.3 iso                                                                           1.32  s     --                                      CH.sub.3                                                                             25.9      CH.sub.3 iso                                                                           1.26  s     --                                      CH.sub.3                                                                             24.6      CH.sub.3 iso                                                                           1.17  s     --                                      CH.sub.3                                                                             24.3      CH.sub.3 iso                                                                           1.17  s     --                                      CH.sub.3                                                                             24.2      H.sub.2 '                                                                              2.16  t     J.sub.2'-3'  = 7.4                      C.sub.1'                                                                             170.6     H.sub.3' 1.48  q     J.sub.3'-4'  = 7.4                      C.sub.2'                                                                             34.9      H.sub.4' 0.76  t     --                                      C.sub.3'                                                                             17.0                                                                   C.sub.4'                                                                             12.5                                                                   ______________________________________                                         (Solvent: CDCl.sub.3 ; chemical shift δ with respect to the TMS         signal).                                                                 

                  TABLE 3                                                         ______________________________________                                        .sup.1 H and .sup.13 C NMR spectra of O-phenylacetyl-2,3:5,6-di-O-isopropy    lidene-                                                                       α-D-mannoside.                                                           ##STR7##                                                                     C      δ (ppm)                                                                           H        δ (ppm)                                                                          J (Hz)                                     ______________________________________                                        C.sub.1                                                                              100.9     H.sub.1  6.11  s    J.sub.1-2 = 0                            C.sub.2                                                                              84.9      H.sub.2  4.63  d    J.sub.2-3 = 5.8                          C.sub.3                                                                              79.3      H.sub.3  4.78  dd   J.sub.3-4 = 3.5                          C.sub.4                                                                              82.4      H.sub.4  3.88  m    J.sub.4-5 = 8.0                          C.sub.5                                                                              72.7      H.sub.5  4.35  m    J.sub.5-6a = 6.2                         C.sub.6                                                                              66.6      H.sub.6a 4.05  dd   J.sub.6a-6b = 8.8                        C.sub.iso                                                                            113.2     H.sub.6b 3.93  m    J.sub.5-6b = 4.4                         C.sub.iso                                                                            109.2     CH.sub.3 iso                                                                           1.43  s    --                                       CH.sub.3                                                                             26.8      CH.sub.3 iso                                                                           1.40  s    --                                       CH.sub.3                                                                             25.9      CH.sub.3 iso                                                                           1.34  s    --                                       CH.sub.3                                                                             25.1      CH.sub.3 iso                                                                           1.29  s    --                                       CH.sub.3                                                                             24.6      H.sub.2' 2.13  s    --                                       C.sub.1'                                                                             169.7     H.sub.4' 7.22  m    --                                       C.sub.2'                                                                             41.3      H.sub.5' to         --                                       C.sub.3'                                                                             133.4     H.sub.6' 7.33       --                                       C.sub.4'                                                                             129.0                                                                  C.sub.5'                                                                             128.6                                                                  C.sub.6'                                                                             127.2                                                                  ______________________________________                                         (Solvent: CDCl.sub.3 ; chemical shift δ with respect to the TMS         signal).                                                                 

                  TABLE 4                                                         ______________________________________                                        .sup.1 H and .sup.13 C NMR spectra of O-3'-phenylpropanoyl-2,3:5,6-di-O-is    o-                                                                            propylidene-α-D-mannoside.                                               ##STR8##                                                                     C      δ (ppm)                                                                           H        δ (ppm)                                                                          J (Hz)                                     ______________________________________                                        C.sub.1                                                                              100.9     H.sub.1  6.08  s    J.sub.1-2 = 0                            C.sub.2                                                                              85.0      H.sub.2  4.54  d    J.sub.2-3 = 5.8                          C.sub.3                                                                              79.2      H.sub.3  4.74  dd   J.sub.3-4 = 3.6                          C.sub.4                                                                              82.3      H.sub.4  3.91  m    J.sub.4-5 = 7.8                          C.sub.5                                                                              72.8      H.sub.5  4.35  m    J.sub.5-6a = 6.2                         C.sub.6                                                                              66.2      H.sub.6a 4.06  dd   J.sub.6a-6b = 8.8                        C.sub.iso                                                                            113.1     H.sub.6b 3.97  m    J.sub.5-6b = 4.5                         C.sub.iso                                                                            109.2     CH.sub.3 iso                                                                           1.44  s    --                                       CH.sub.3                                                                             26.8      CH.sub.3 iso                                                                           1.42  s    --                                       CH.sub.3                                                                             26.6      CH.sub.3 iso                                                                           1.34  s    --                                       CH.sub.3                                                                             25.1      CH.sub.3 iso                                                                           1.29  s    --                                       CH.sub.3                                                                             24.9      H.sub.2' 2.92  t    J.sub.2'-3'  = 7.4                       C.sub.1'                                                                             171.1     H.sub.3' 2.62  t    --                                       C.sub.2'                                                                             35.9      H.sub.5' 7.27  m    --                                       C.sub.3'                                                                             30.7      H.sub.6' to         --                                       C.sub.4'                                                                             140.0     H.sub.7' 7.18       --                                       C.sub.5'                                                                             128.4                                                                  C.sub.6'                                                                             128.1                                                                  C.sub.7'                                                                             126.3                                                                  ______________________________________                                         (Solvent: CDCl.sub.3 ; chemical shift δ with respect to the TMS         signal).                                                                 

                  TABLE 5                                                         ______________________________________                                        .sup.1 H and .sup.13 C NMR spectra of O-4'-phenylbutanoyl-2,3:5,6-di-O-iso    propylidene-α-D-mannoside.                                               ##STR9##                                                                     C      δ (ppm)                                                                           H        δ (ppm)                                                                          J (Hz)                                     ______________________________________                                        C.sub.1                                                                              100.7     H.sub.1  6.11  s    J.sub.1-2 = 0                            C.sub.2                                                                              85.0      H.sub.2  4.66  d    J.sub.2-3 = 5.8                          C.sub.3                                                                              79.3      H.sub.3  4.84  dd   J.sub.3-4 = 3.6                          C.sub.4                                                                              82.3      H.sub.4  4.01  m    J.sub.4-5 = 7.8                          C.sub.5                                                                              72.8      H.sub.5  4.40  m    J.sub.5-6a = 6.1                         C.sub.6                                                                              66.7      H.sub.6a 4.09  dd   J.sub.6a-6b = 8.7                        C.sub.iso                                                                            113.2     H.sub.6b 4.03  m    J.sub.5-6b = 4.8                         C.sub.iso                                                                            109.2     CH.sub.3 iso                                                                           1.45  s    --                                       CH.sub.3                                                                             26.8      CH.sub.3 iso                                                                           1.42  s    --                                       CH.sub.3                                                                             26.0      CH.sub.3 iso                                                                           1.34  s    --                                       CH.sub.3                                                                             25.1      CH.sub.3 iso                                                                           1.30  s    --                                       CH.sub.3                                                                             24.6      H.sub.2' 2.62  t    J.sub.2'-3'  = 7.7                       C.sub.1'                                                                             171.6     H.sub.3' 1.92  t    J.sub.3'-4'  = 7.4                       C.sub.2'                                                                             34.9      H.sub.4' 2.29       --                                       C.sub.3'                                                                             33.4      H.sub.6' 7.29  m    --                                       C.sub.4'                                                                             25.9      H.sub.7' to         --                                       C.sub.5'                                                                             141.0     H.sub.8' 7.13       --                                       C.sub.6'                                                                             128.3                                                                  C.sub.7'                                                                             126.3                                                                  C.sub.8'                                                                             126.0                                                                  ______________________________________                                         (Solvent: CDCl.sub.3 ; chemical shift δ with respect to the TMS         signal).                                                                 

                  TABLE 6                                                         ______________________________________                                        .sup.1 H and .sup.13 C NMR spectra of O-n-butanoyl-2,3-O-isopropylidene-.a    lpha.-D-                                                                      mannoside.                                                                     ##STR10##                                                                    C      δ (ppm)                                                                           H        δ (ppm)                                                                          J (Hz)                                     ______________________________________                                        C.sub.1                                                                              99.4      H.sub.1  6.05  s    J.sub.1-2 = 0                            C.sub.2                                                                              83.7      H.sub.2  4.58  d    J.sub.2-3 = 5.9                          C.sub.3                                                                              78.7      H.sub.3  4.81  dd   J.sub.3-4 = 3.4                          C.sub.4                                                                              80.3      H.sub.4  3.94  dd   J.sub.4-5 = 8.5                          C.sub.5                                                                              68.8      H.sub.5  3.91  m    J.sub.5-6a = 7.9                         C.sub.6                                                                              63.1      H.sub.6a 3.73  dd   J.sub.6a-6b = n.d.                       C.sub.iso                                                                            112.2     H.sub.6b 3.59  dd   J.sub.5-6b = n.d.                        CH.sub.3                                                                             24.9      CH.sub.3 iso                                                                           1.38  s    --                                       CH.sub.3                                                                             23.7      CH.sub.3 iso                                                                           1.24  s    --                                       C.sub.1'                                                                             171.1     H.sub.2 '                                                                              2.17  t    J.sub.2'-3'  = 7.4                       C.sub.2'                                                                             35.1      H.sub.3' 1.53  q    J.sub.3'-4'  = 7.4                       C.sub.3'                                                                             17.2      H.sub.4' 0.83  t    --                                       C.sub.4'                                                                             12.5      OH       3.33  s    --                                                        OH       2.85  s    --                                       ______________________________________                                         (Solvent: CDCl.sub.3 ; chemical shift δ with respect to the TMS         signal).                                                                 

                  TABLE 7                                                         ______________________________________                                        .sup.1 H and .sup.13 C NMR spectra of O-phenylacetyl-2,3-O-isopropylidene-    α-D-                                                                    mannoside.                                                                     ##STR11##                                                                    C      δ (ppm)                                                                           H        δ (ppm)                                                                          J (Hz)                                     ______________________________________                                        C.sub.1                                                                              100.6     H.sub.1  6.15  s    J.sub.1-2 = 0                            C.sub.2                                                                              84.6      H.sub.2  4.55  d    J.sub.2-3 = 5.9                          C.sub.3                                                                              79.6      H.sub.3  4.80  dd   J.sub.3-4 = 2.5                          C.sub.4                                                                              81.3      H.sub.4  4.00  m    J.sub.4-5 = 7.7                          C.sub.5                                                                              69.8      H.sub.5  3.95  m    J.sub.5-6a = 2.4                         C.sub.6                                                                              64.1      H.sub.6a 3.83  dd   J.sub.6a-6b = 11.5                       C.sub.iso                                                                            113.1     H.sub.6b 3.62  m    J.sub.5-6b = 4.7                         CH.sub.3                                                                             26.0      CH.sub.3 iso                                                                           1.45  s    --                                       CH.sub.3                                                                             24.7      CH.sub.3 iso                                                                           1.28  s    --                                       C.sub.1'                                                                             171.5     H.sub.2' 2.92  s    --                                       C.sub.2'                                                                             41.3      H.sub.4' 7.25  m    --                                       C.sub.3'                                                                             133.7     H.sub.5' to         --                                       C.sub.4'                                                                             128.4     H.sub.6' 7.12       --                                       C.sub.5'                                                                             128.2     OH.sub.5,6                                                                             2.80  m    --                                       C.sub.6'                                                                             125.9                                                                  ______________________________________                                         (Solvent: CDCl.sub.3 ; chemical shift δ with respect to the TMS         signal).                                                                 

                  TABLE 8                                                         ______________________________________                                        .sup.1 H and .sup.13 C NMR spectra of O-3'-phenylpropanoyl-2,3-O-isopropyl    idene-                                                                        α-D-mannoside.                                                           ##STR12##                                                                    C      δ (ppm)                                                                           H        δ (ppm)                                                                          J (Hz)                                     ______________________________________                                        C.sub.1                                                                              100.6     H.sub.1  6.10  s    J.sub.1-2 = 0                            C.sub.2                                                                              84.7      H.sub.2  4.50  d    J.sub.2-3 = 5.8                          C.sub.3                                                                              79.7      H.sub.3  4.77  dd   J.sub.3-4 = 2.6                          C.sub.4                                                                              81.3      H.sub.4  3.94  m    J.sub.4-5 = 7.9                          C.sub.5                                                                              69.9      H.sub.5  3.91  m    J.sub.5-6a = 2.3                         C.sub.6                                                                              64.0      H.sub.6a 3.77  dd   J.sub.6a-6b = 11.5                       C.sub.iso                                                                            113.2     H.sub.6b 3.61  m    J.sub.5-6b = 4.6                         CH.sub.3                                                                             25.9      CH.sub.3 iso                                                                           1.44  s    --                                       CH.sub.3                                                                             24.7      CH.sub.3 iso                                                                           1.29  s    --                                       C.sub.1'                                                                             171.1     H.sub.2' 2.90  t    J.sub.2'-3'  = 7.5                       C.sub.2'                                                                             35.7      H.sub.3' 2.60  t    --                                       C.sub.3'                                                                             30.6      H.sub.5' 7.27  m    --                                       C.sub.4'                                                                             140.0     H.sub.6' to         --                                       C.sub.5'                                                                             128.4     H.sub.7' 7.03       --                                       C.sub.6'                                                                             128.2     OH.sub.5,6                                                                             3.15  m    --                                       C.sub.7'                                                                             126.3                                                                  ______________________________________                                         (Solvent: CDCl.sub.3 ; chemical shift δ with respect to the TMS         signal).                                                                 

                  TABLE 9                                                         ______________________________________                                        .sup.1 H and .sup.13 C NMR spectra of O-4'-phenylbutanoyl-2,3-O-isopropyli    dene-                                                                         α-D-mannoside.                                                           ##STR13##                                                                    C      δ (ppm)                                                                           H        δ (ppm)                                                                          J (Hz)                                     ______________________________________                                        C.sub.1                                                                              100.5     H.sub.1  6.16  s    J.sub.1-2 = 0                            C.sub.2                                                                              84.8      H.sub.2  4.64  d    J.sub.2-3 = 5.9                          C.sub.3                                                                              79.7      H.sub.3  4.86  dd   J.sub.3-4 = 3.5                          C.sub.4                                                                              81.3      H.sub.4  4.03  m    J.sub.4-5 = 8.3                          C.sub.5                                                                              69.9      H.sub.5  3.98  m    J.sub.5-6a = 2.8                         C.sub.6                                                                              64.0      H.sub.6a 3.81  dd   J.sub.6a-6b = 11.5                       C.sub.iso                                                                            113.2     H.sub.6b 4.62  m    J.sub.5-6b = 5.3                         CH.sub.3                                                                             26.0      CH.sub.3 iso                                                                           1.45  s    --                                       CH.sub.3                                                                             24.7      CH.sub.3 iso                                                                           1.30  s    --                                       C.sub.1'                                                                             171.7     H.sub.2' 2.60  t    J.sub.2'-3'  = 7.5                       C.sub.2'                                                                             34.9      H.sub.3' 1.91  t    J.sub.3'-4'  = 7.4                       C.sub.3'                                                                             33.4      H.sub.4' 2.27       --                                       C.sub.4'                                                                             25.9      H.sub.6' 7.27  m    --                                       C.sub.5'                                                                             141.0     H.sub.7' to         --                                       C.sub.6'                                                                             128.3     H.sub.8' 7.11       --                                       C.sub.7'                                                                             128.3     OH.sub.5,6                                                                             3.35  m                                             C.sub.8'                                                                             126.0                                                                  ______________________________________                                         (Solvent: CDCl.sub.3 ; chemical shift δ with respect to the TMS         signal).                                                                 

                  TABLE 10                                                        ______________________________________                                        .sup.1 H and .sup.13 C NMR spectra of 1-O-n-butanoyl-2,3:4,5-di-O-isopropy    l-                                                                            idenexylitol.                                                                  ##STR14##                                                                    C    δ (ppm)                                                                            H        δ (ppm)                                                                           J (Hz)                                     ______________________________________                                        C.sub.1                                                                            63.9       H.sub.1a 4.28  dd    J.sub.1a-21b = 11.0                      C.sub.2                                                                            75.3       H.sub.1b 4.07  dd    J.sub.1a-2 = 2.6                                                              J.sub.1b-2 = 5.5                         C.sub.3                                                                            77.4       H.sub.2  4.12  m     J.sub.2-3 = 7.3                          C.sub.4                                                                            74.8       H.sub.3  3.85  dd    J.sub.3-4 = 4.5                          C.sub.5                                                                            65.4       H.sub.4  4.18  ddd   J.sub.4-5a = 8.0                         C.sub.iso                                                                          109.9      H.sub.5a 4.03  dd    J.sub.5a-5b = 7.7                        C.sub.iso                                                                          109.6      H.sub.5b 3.83  dd    J.sub.4-5b = 6.7                         CH.sub.3                                                                           26.9       CH.sub.3 iso                                                                           1.37  s     --                                       CH.sub.3                                                                           26.8       CH.sub.3 iso                                                                           1.35  s     --                                       CH.sub.3                                                                           26.0       CH.sub.3 iso                                                                           1.35  s     --                                       CH.sub.3                                                                           25.2       CH.sub.3 iso                                                                           1.30  s     --                                       C.sub.1'                                                                           173.0      H.sub.2 '                                                                              2.28  t     J.sub.2'-3'  = 7.4                       C.sub.2'                                                                           35.8       H.sub.3' 1.55  q     J.sub.3'-4'  = 7.3                       C.sub.3'                                                                           18.2       H.sub.4' 0.88  t     --                                       C.sub.4'                                                                           13.4                                                                     ______________________________________                                         (Solvent: CDCl.sub.3 ; chemical shift δ with respect to the TMS         signal).                                                                 

                  TABLE 11                                                        ______________________________________                                        .sup.1 H and .sup.13 C NMR spectra of 1-O-phenylacetyl-2,3:4,5-di-O-isopro    pyl-                                                                          idenexylitol.                                                                  ##STR15##                                                                    C    δ (ppm)                                                                            H        δ (ppm)                                                                           J (Hz)                                     ______________________________________                                        C.sub.1                                                                            64.4       H.sub.1a 4.21  dd    J.sub.1a-21b = 11.0                      C.sub.2                                                                            77.4       H.sub.1b 4.01  dd    J.sub.1a-2 = 2.5                                                              J.sub.1b-2 = 5.7                         C.sub.3                                                                            75.1       H.sub.2  4.04  m     J.sub.2-3 = 7.3                          C.sub.4                                                                            74.7       H.sub.3  3.71  dd    J.sub.3-4 = 3.9                          C.sub.5                                                                            65.5       H.sub.4  4.08  ddd   J.sub.4-5a = 8.1                         C.sub.iso                                                                          110.0      H.sub.5a 3.88  dd    J.sub.5a-5b = 7.2                        C.sub.iso                                                                          109.7      H.sub.5b 3.73  dd    J.sub.4-5b = 6.7                         CH.sub.3                                                                           26.9       CH.sub.3 iso                                                                           1.38  s     --                                       CH.sub.3                                                                           26.8       CH.sub.3 iso                                                                           1.36  s     --                                       CH.sub.3                                                                           26.0       CH.sub.3 iso                                                                           1.33  s     --                                       CH.sub.3                                                                           25.3       CH.sub.3 iso                                                                           1.32  s     --                                       C.sub.1'                                                                           171.0      H.sub.2 '                                                                              2.11  s     --                                       C.sub.2'                                                                           41.1       H.sub.4' 7.29  m     --                                       C.sub.3'                                                                           133.6      H.sub.5' to          --                                       C.sub.4'                                                                           129.2      H.sub.6' 7.15        --                                       C.sub.5'                                                                           128.5                                                                    C.sub.6'                                                                           127.1                                                                    ______________________________________                                         (Solvent: CDCl.sub.3 ; chemical shift δ with respect to the TMS         signal).                                                                 

                  TABLE 12                                                        ______________________________________                                        .sup.1 H and .sup.13 C NMR spectra of 1-O-3'-phenylpropanoyl-2,3:4,5-di-O-    iso-                                                                          propylidenexylitol.                                                            ##STR16##                                                                    C    δ (ppm)                                                                            H        δ (ppm)                                                                           J (Hz)                                     ______________________________________                                        C.sub.1                                                                            64.1       H.sub.1a 4.24  dd    J.sub.1a-21b = 11.3                      C.sub.2                                                                            77.3       H.sub.1b 4.08  dd    J.sub.1a-2 = 2.7                                                              J.sub.1b-2 = 6.5                         C.sub.3                                                                            75.2       H.sub.2  4.10  m     J.sub.2-3 = 7.9                          C.sub.4                                                                            74.8       H.sub.3  3.78  dd    J.sub.3-4 = 4.2                          C.sub.5                                                                            65.4       H.sub.4  4.13  ddd   J.sub.4-5a = 8.1                         C.sub.iso                                                                          110.0      H.sub.5a 3.99  dd    J.sub.5a-5b = 7.1                        C.sub.iso                                                                          109.7      H.sub.5b 3.79  dd    J.sub.4-5b = 6.7                         CH.sub.3                                                                           26.9       CH.sub.3 iso                                                                           1.37  s     --                                       CH.sub.3                                                                           26.9       CH.sub.3 iso                                                                           1.36  s     --                                       CH.sub.3                                                                           26.0       CH.sub.3 iso                                                                           1.35  s     --                                       CH.sub.3                                                                           25.3       CH.sub.3 iso                                                                           1.31  s     --                                       C.sub.1'                                                                           172.4      H.sub.2 '                                                                              2.92  t     J.sub.2'-3'  = 7.6                       C.sub.2'                                                                           35.6       H.sub.3' 2.65  q     --                                       C.sub.3'                                                                           30.8       H.sub.5' 7.27  t     --                                       C.sub.4'                                                                           140.2      H.sub.6' to    q     --                                       C.sub.5'                                                                           128.4      H.sub.7' 7.14  t     --                                       C.sub.6'                                                                           128.1                                                                    C.sub.7'                                                                           126.2                                                                    ______________________________________                                         (Solvent: CDCl.sub.3 ; chemical shift δ with respect to the TMS         signal).                                                                 

                  TABLE 13                                                        ______________________________________                                        .sup.1 H and .sup.13 C NMR spectra of 1-O-4'-phenylbutanoyl-2,3:4,5-di-O-i    so-                                                                           propylidenexylitol.                                                            ##STR17##                                                                    C    δ (ppm)                                                                            H        δ (ppm)                                                                           J (Hz)                                     ______________________________________                                        C.sub.1                                                                            64.1       H.sub.1a 4.26  dd    J.sub.1a-21b = 11.2                      C.sub.2                                                                            77.4       H.sub.1b 4.07  dd    J.sub.1a-2 = 2.8                                                              J.sub.1b-2 = 5.7                         C.sub.3                                                                            75.3       H.sub.2  4.13  m     J.sub.2-3 = 8.0                          C.sub.4                                                                            74.8       H.sub.3  3.84  dd    J.sub.3-4 = 4.4                          C.sub.5                                                                            65.5       H.sub.4  4.16  ddd   J.sub.4-5a = 5.7                         C.sub.iso                                                                          110.0      H.sub.5a 4.02  dd    J.sub.5a-5b = 7.8                        C.sub.iso                                                                          109.7      H.sub.5b 3.83  dd    J.sub.4-5b = 6.7                         CH.sub.3                                                                           26.9       CH.sub.3 iso                                                                           1.40  s     --                                       CH.sub.3                                                                           26.3       CH.sub.3 iso                                                                           1.38  s     --                                       CH.sub.3                                                                           26.0       CH.sub.3 iso                                                                           1.37  s     --                                       CH.sub.3                                                                           25.3       CH.sub.3 iso                                                                           1.34  s     --                                       C.sub.1'                                                                           172.9      H.sub.2 '                                                                              2.62  t     J.sub.2'-3'  = 7.6                       C.sub.2'                                                                           35.0       H.sub.3' 1.93  q     J.sub.3'-4'  = 7.5                       C.sub.3'                                                                           33.3       H.sub.4' 2.34  t     --                                       C.sub.4'                                                                           26.9       H.sub.6' 7.27  m     --                                       C.sub.5'                                                                           141.1      H.sub.7' to          --                                       C.sub.6'                                                                           128.3      H.sub.8' 7.12        --                                       C.sub.7'                                                                           128.3                                                                    C.sub.8'                                                                           125.9                                                                    ______________________________________                                         (Solvent: CDCl.sub.3 ; chemical shift δ with respect to the TMS         signal).                                                                 

                  TABLE 14                                                        ______________________________________                                        .sup.1 H and .sup.13 C NMR spectra of 1-O-n-butanoyl-2,3-O-isopropylidenex    ylitol.                                                                        ##STR18##                                                                    C    δ (ppm)                                                                            H        δ (ppm)                                                                           J (Hz)                                     ______________________________________                                        C.sub.1                                                                            65.8       H.sub.1a 4.26  dd    J.sub.1a-21b = 11.6                      C.sub.2                                                                            77.2       H.sub.1b 4.08  dd    J.sub.1a-2 = 3.5                                                              J.sub.1b-2 = 4.3                         C.sub.3                                                                            77.3       H.sub.2  4.20  ddd   J.sub.2-3 = 7.9                          C.sub.4                                                                            68.3       H.sub.3  3.83  dd    J.sub.3-4 = 3.0                          C.sub.5                                                                            64.7       H.sub.4  3.65  ddd   J.sub.4-5a = 3.9                         C.sub.iso                                                                          109.5      H.sub.5a 3.74  dd    J.sub.5a-5b = 12.0                       CH.sub.3                                                                           26.1       H.sub.5b 3.61  dd    J.sub.4-5b = 4.0                         CH.sub.3                                                                           25.9       CH.sub.3 iso                                                                           1.37  s     --                                       C.sub.1'                                                                           172.3      CH.sub.3 iso                                                                           1.36  s     --                                       C.sub.2'                                                                           35.0       H.sub.2 '                                                                              2.30  t     J.sub.2'-3'  = 7.3                       C.sub.3'                                                                           17.3       H.sub.3' 1.60  q     J.sub.3'-4'  = 6.3                       C.sub.4'                                                                           12.6       H.sub.4' 0.89  t     --                                                       OH.sub.4,5                                                                             2.56  s     --                                       ______________________________________                                         (Solvent: CDCl.sub.3 ; chemical shift δ with respect to the TMS         signal).                                                                 

                  TABLE 15                                                        ______________________________________                                        .sup.1 H and .sup.13 C NMR spectra of 1-O-n-butanoylxylitol.                   ##STR19##                                                                    C   δ (ppm)                                                                            H        δ (ppm)                                                                            J (Hz)                                     ______________________________________                                        C.sub.1                                                                            66.9      H.sub.1a 4.52   dd    J.sub.1a-21b = 11.1                      C.sub.2                                                                            72.3      H.sub.1b 4.47   dd    J.sub.1a-2 = 6.7                                                              J.sub.1b-2 = 4.7                         C.sub.3                                                                            74.0      H.sub.2  4.36   ddd   J.sub.2-3 = 3.8                          C.sub.4                                                                            71.4      H.sub.3  4.25   dd    J.sub.3-4 = 5.5                          C.sub.5                                                                            64.4      H.sub.4  4.21   m     J.sub.4-5a = 3.6                         C.sub.1'                                                                           173.0     H.sub.5a 4.09   dd    J.sub.5a-5b = n.d.                       C.sub.2'                                                                           36.2      H.sub.5b 4.09   dd    J.sub.4-5b = 6.0                         C.sub.3'                                                                           18.7      H.sub.2 '                                                                              1.88   t     J.sub.2'-3'  = 7.3                       C.sub.4'                                                                           13.7      H.sub.3' 1.22   q     J.sub.3'-4'  = 7.3                                      H.sub.4' 0.44   t     --                                                      OH.sub.2-5                                                                             5.5-6.4                                                                              m     --                                       ______________________________________                                         (Solvent: C.sub.5 D.sub.5 N; chemical shift δ with respect to the       TMS signal).                                                             

                  TABLE 16                                                        ______________________________________                                        .sup.1 H and .sup.13 C NMR spectra of 1-O-phenylacetyl-2,3-O-isopropyliden    e-                                                                            xylitol.                                                                       ##STR20##                                                                    C    δ (ppm)                                                                            H        δ (ppm)                                                                           J (Hz)                                     ______________________________________                                        C.sub.1                                                                            64.5       H.sub.1a 4.28  dd    J.sub.1a-21b = 11.5                      C.sub.2                                                                            74.9       H.sub.1b 4.12  dd    J.sub.1a-2 = 3.5                                                              J.sub.1b-2 = 4.5                         C.sub.3                                                                            78.9       H.sub.2  4.19  m     J.sub.2-3 = 7.9                          C.sub.4                                                                            69.7       H.sub.3  3.78  dd    J.sub.3-4 = 2.6                          C.sub.5                                                                            64.0       H.sub.4  3.63  ddd   J.sub.4-5a = n.d.                        C.sub.iso                                                                          109.9      H.sub.5a 3.60  dd    J.sub.5a-5b = 8.0                        CH.sub.3                                                                           26.9       H.sub.5b 3.53  dd    J.sub.4-5b = 3.9                         CH.sub.3                                                                           26.8       CH.sub.3 iso                                                                           1.33  s     --                                       C.sub.1'                                                                           171.2      CH.sub.3 iso                                                                           1.35  s     --                                       C.sub.2'                                                                           41.1       H.sub.2 '                                                                              2.37  s     --                                       C.sub.3'                                                                           133.6      H.sub.4' 7.30  m     --                                       C.sub.4'                                                                           129.2      H.sub.5' to          --                                       C.sub.5'                                                                           128.5      H.sub.6' 7.22        --                                       C.sub.6'                                                                           127.1      OH.sub.4,5                                                                             2.7   m     --                                       ______________________________________                                         (Solvent: CDCl.sub.3 ; chemical shift δ with respect to the TMS         signal).                                                                 

                  TABLE 17                                                        ______________________________________                                        .sup.1 H and .sup.13 C NMR spectra of 1-O-phenylacetylxylitol.                 ##STR21##                                                                    C     δ (ppm)                                                                           H        δ (ppm)                                                                           J (Hz)                                     ______________________________________                                        C.sub.1                                                                             67.8      H.sub.1a 4.75  dd    J.sub.1a-21b = 11.2                      C.sub.2                                                                             72.6      H.sub.1b 4.70  dd    J.sub.1a-2 = 7.3                                                              J.sub.1b-2 = 4.8                         C.sub.3                                                                             74.2      H.sub.2  4.56+ m     J.sub.2-3 = 3.7                          C.sub.4                                                                             71.6      H.sub.3  4.43  dd    J.sub.3-4 = 4.8                          C.sub.5                                                                             64.8      H.sub.4  4.40  ddd   J.sub.4-5a = 3.1                         C.sub.1'                                                                            172.1     H.sub.5a 4.26  dd    J.sub.5a-5b = n.d.                       C.sub.2'                                                                            41.7      H.sub.5b 4.21  dd    J.sub.4-5b = 5.1                         C.sub.3'                                                                            135.4     H.sub.2 '                                                                              1.94  s     --                                       C.sub.4'                                                                            130.2     H.sub.4' 7.33  m     --                                       C.sub.5'                                                                            129.2     H.sub.5' to          --                                       C.sub.6'                                                                            127.6     H.sub.6' 7.13        --                                                       OH.sub.2,5                                                                             6.11  m     --                                       ______________________________________                                         (Solvent: C.sub.5 D.sub.5 N; chemical shift δ with respect to the       TMS signal).                                                             

                  TABLE 18                                                        ______________________________________                                        .sup.1 H and .sup.13 C NMR spectra of 1-O-3'-phenylpropanoyl-2,3-O-iso-       propylidenexylitol.                                                            ##STR22##                                                                    C    δ (ppm)                                                                            H        δ (ppm)                                                                           J (Hz)                                     ______________________________________                                        C.sub.1                                                                            64.5       H.sub.1a 4.29  dd    J.sub.1a-21b = 11.2                      C.sub.2                                                                            75.1       H.sub.1b 4.16  dd    J.sub.1a-2 = 3.6                                                              J.sub.1b-2 = 1.4                         C.sub.3                                                                            77.9       H.sub.2  4.23  m     J.sub.2-3 = 7.3                          C.sub.4                                                                            69.8       H.sub.3  3.82  dd    J.sub.3-4 = 3.0                          C.sub.5                                                                            63.7       H.sub.4  3.69  ddd   J.sub.4-5a = 7.0                         C.sub.iso                                                                          110.0      H.sub.5a 3.71  dd    J.sub.5a-5b = 7.9                        CH.sub.3                                                                           26.8       H.sub.5b 3.63  dd    J.sub.4-5b = 4.3                         CH.sub.3                                                                           26.4       CH.sub.3 iso                                                                           1.38  s     --                                       C.sub.1'                                                                           172.4      CH.sub.3 iso                                                                           1.36  s     --                                       C.sub.2'                                                                           35.5       H.sub.2 '                                                                              2.91  t     J.sub.2'-3'  = 7.7                       C.sub.3'                                                                           30.7       H.sub.3' 2.64  t     --                                       C.sub.4'                                                                           140.2      H.sub.5' 7.27  m     --                                       C.sub.5'                                                                           128.4      H.sub.6' to          --                                       C.sub.6'                                                                           128.2      H.sub.7' 7.14        --                                       C.sub.7'                                                                           126.2      OH.sub.4,5                                                                             4.16  m     --                                       ______________________________________                                         (Solvent: CDCl.sub.3 ; chemical shift δ with respect to the TMS         signal).                                                                 

                  TABLE 19                                                        ______________________________________                                        .sup.1 H and .sup.13 C NMR spectra of 1-O-(3'-phenylpropanoyl)xylitol.         ##STR23##                                                                    C     δ (ppm)                                                                           H        δ (ppm)                                                                           J (Hz)                                     ______________________________________                                        C.sub.1                                                                             67.4      H.sub.1a 4.66  dd    J.sub.1a-21b = 10.7                      C.sub.2                                                                             72.6      H.sub.1b 4.63  dd    J.sub.1a-2 = 7.2                                                              J.sub.1b-2 = 4.5                         C.sub.3                                                                             74.3      H.sub.2  4.49  m     J.sub.2-3 = 3.7                          C.sub.4                                                                             71.7      H.sub.3  4.38  dd    J.sub.3-4 = 4.9                          C.sub.5                                                                             64.8      H.sub.4  4.36  ddd   J.sub.4-5a = 3.3                         C.sub.1'                                                                            173.3     H.sub.5a 4.22  dd    J.sub.5a-5b = n.d.                       C.sub.2'                                                                            36.3      H.sub.5b 4.18  dd    J.sub.4-5b = 5.6                         C.sub.3'                                                                            30.9      H.sub.2 '                                                                              2.87  t     J.sub.2'-3'  = 7.7                       C.sub.4'                                                                            141.6     H.sub.3' 2.60  t     --                                       C.sub.5'                                                                            129.2     H.sub.5' 7.23  m     --                                       C.sub.6'                                                                            129.0     H.sub.6' to          --                                       C.sub.7'                                                                            126.9     H.sub.7' 7.09        --                                                       OH.sub.2,5                                                                             6.04  m     --                                       ______________________________________                                         (Solvent: C.sub.5 D.sub.5 N; chemical shift δ with respect to the       TMS signal).                                                             

                  TABLE 20                                                        ______________________________________                                        .sup.1 H and .sup.13 C NMR spectra of 1-O-4'-phenylbutanoyl-2,3-O-iso-        propylidenexylitol.                                                            ##STR24##                                                                    C    δ (ppm)                                                                            H        δ (ppm)                                                                           J (Hz)                                     ______________________________________                                        C.sub.1                                                                            64.4       H.sub.1a 4.44  dd    J.sub.1a-21b = 11.2                      C.sub.2                                                                            75.2       H.sub.1b 4.10  dd    J.sub.1a-2 = 3.5                                                              J.sub.1b-2 = 5.3                         C.sub.3                                                                            78.8       H.sub.2  4.21  m     J.sub.2-3 = 8.0                          C.sub.4                                                                            70.0       H.sub.3  3.84  dd    J.sub.3-4 = 2.0                          C.sub.5                                                                            63.8       H.sub.4  3.68  ddd   J.sub.4-5a = n.d.                        C.sub.iso                                                                          110.0      H.sub.5a 3.68  dd    J.sub.5a-5b = 3.2                        CH.sub.3                                                                           26.8       H.sub.5b 3.65  dd    J.sub.4-5b = n.d.                        CH.sub.3                                                                           26.2       CH.sub.3 iso                                                                           1.38  s     --                                       C.sub.1'                                                                           173.1      CH.sub.3 iso                                                                           1.36  s     --                                       C.sub.2'                                                                           35.0       H.sub.2 '                                                                              2.60  t     J.sub.2'-3'  = 7.5                       C.sub.3'                                                                           33.3       H.sub.3' 1.93  q     J.sub.3'-4'  = 7.6                       C.sub.4'                                                                           26.9       H.sub.4' 2.32  t     --                                       C.sub.5'                                                                           141.1      H.sub.6' 7.26  m     --                                       C.sub.6'                                                                           128.3      H.sub.7' to          --                                       C.sub.7'                                                                           128.3      H.sub.8' 7.11        --                                       C.sub.8'                                                                           125.9      OH.sub.4,5                                                                             4.15  m     --                                       ______________________________________                                         (Solvent: CDCl.sub.3 ; chemical shift δ with respect to the TMS         signal).                                                                 

                  TABLE 21                                                        ______________________________________                                        .sup.1 H and .sup.13 C NMR spectra of 1-O-(4'-phenylbutanoyl)xylitol.          ##STR25##                                                                    C     δ (ppm)                                                                           H        δ (ppm)                                                                           J (Hz)                                     ______________________________________                                        C.sub.1                                                                             67.3      H.sub.1a 4.75  dd    J.sub.1a-21b = 11.2                      C.sub.2                                                                             72.6      H.sub.1b 4.69  dd    J.sub.1a-2 = 7.2                                                              J.sub.1b-2 = 4.5                         C.sub.3                                                                             74.3      H.sub.2  4.56  m     J.sub.2-3 = 3.7                          C.sub.4                                                                             71.7      H.sub.3  4.43  dd    J.sub.3-4 = 5.0                          C.sub.5                                                                             64.8      H.sub.4  4.40  ddd   J.sub.4-5a = 3.5                         C.sub.1 '                                                                           173.9     H.sub.5a 4.28  dd    J.sub.5a-5b = n.d.                       C.sub.2 '                                                                           35.6      H.sub.5b 4.22  dd    J.sub.4-5b = 5.4                         C.sub.3 '                                                                           34.6      H.sub.2 '                                                                              2.52  t     J.sub.2'-3'  = 7.7                       C.sub.4 '                                                                           27.3      H.sub.3 '                                                                              1.87  q     J.sub.3'-4'  = 7.0                       C.sub.5 '                                                                           142.4     H.sub.4 '                                                                              2.30  t     --                                       C.sub.6 '                                                                           129.2     H.sub.6 '                                                                              7.25  m     --                                       C.sub.7 '                                                                           129.1     H.sub.7 '                                                                              to          --                                       C.sub.8 '                                                                           126.6     H.sub.8 '                                                                              7.10        --                                                       OH.sub.2,5                                                                             5.92  m     --                                       ______________________________________                                         (Solvent: C.sub.5 D.sub.5 N; chemical shift δ with respect to the       TMS signal).                                                             

We claim:
 1. A monoester of a carboxylic acid selected from the group consisting of phenylacetic acid, 3-phenylpropionic acid, 4-phenylbutyric acid and n-butyric acid and a member selected from the group consisting of monosaccharides and sugar alcohols of the formula Su(OH)₅, said monoester having the formula: ##STR26## wherein R₁ CO is the acyl of the carboxylic acid, R₂, R₃, R₄ and R₅ are individually selected from the group consisting of hydrogen, optionally unsaturated, optionally cyclic hydrocarbons or R₂ and R₃ or R₄ and R₅ form an acetal ##STR27## with R--C--R¹ being selected from the group consisting of phenylmethylene, methylene, cyclohexylidene and isopropylidene with at least two of R₂, R₃, R₄ and R₅ being hydrogen and Su(OH)₅ or said corresponding monoester has a structure that prevents internal transesterification and the ester is bonded to an anomeric carbon atom or a C₁ primary carbon atom, with the proviso that when R₁ CO is n-butanoyl, the monosaccharide or itol is other than D-galactose or D-glucose or glycerol.
 2. A monoester of claim 1 wherein Su(OH)₅ precursor is selected from the group consisting of D-mannose and xylitol.
 3. A monoester of claim 2 selected from the group consisting of 1-O-acyl-2,3-O-acetal-xylitol and 1-O-acyl-xylitol and the acyl is derived from a carboxylic acid selected from the group consisting of phenylacetic acid, 3-phenylpropionic acid, 4-phenylbutyric acid and n-butyric acid.
 4. A monoester of claim 1 wherein R₂ and R₃ or R₄ and R₅ form an acetal and R and R' together with the carbon to which they are attached form a member selected from the group consisting of phenylmethylene, methylene, cyclohexylidene and isopropylidene.
 5. A monoester of claim 1 selected from the group consisting of α- and β-O-acyl-2,3-acetal of D-mannosides and α-and β-O-acyl-D-mannosides and the acyl is derived from a carboxylic acid selected from the group consisting of phenylacetic acid, 3-phenylpropionic acid, 4-phenylbutyric acid and n-butyric acid.
 6. A monoester of claim 1 selected from the group consisting of α-O-n-butanoyl-D-mannoside and α-O-n-butanoyl-2,3,O-isopropylidene-D-mannoside.
 7. A monoester of claim 1 selected from the group consisting of α-O-phenylacetyl-D-mannoside and α-O-phenylacetyl-2,3-O-isopropylidene-D-mannoside.
 8. A monoester of claim 1 selected from the group consisting of α-O-3'-phenylpropanoyl-D-mannoside and a α-O-3'-phenylpropanoyl-2,3-O-isopropylidene-D-mannoside.
 9. A monoester of claim 1 selected from the group consisting of α-O-4-phenylbutanoyl-D-mannoside and α-O-4-phenylbutanoyl-2,3-O-isopropylidene-D-mannoside.
 10. A monoester of claim 1 selected from the group consisting of 1-O-n-butanoyl-xylitol and 1-O-n-butanoyl-2,3-O-isopropylidene-xylitol.
 11. A monoester of claim 1 selected from the group consisting of 1-O-phenylacetyl-xylitol and 1-O-phenylacetyl-2,3-O-isopropylidene-xylitol.
 12. A monoester of claim 1 selected from the group consisting of 1-O-(3-phenylpropanoyl)-xylitol and 1-O-(3-phenylpropanoyl)-2,3-O-isopropylidene-xylitol.
 13. A monoester of claim 1 selected from the group consisting of 1-O-(4-phenylbutanoyl)-xylitol and 1-O-(4-phenylbutanoyl)-2,3-O-isopropylidene-xylitol.
 14. A method of treating heamoglobin insufficiencies in warm-blooded animals comprising administering to warm-blooded animals in need thereof an amount of a monoester of claim 1 sufficient to treat heamoglobin insufficiency.
 15. The method of claim 14 wherein the Su(OH)₅ precursor is selected from the group consisting of D-mannose and xylitol.
 16. A method of treating premalignant and malignant tumors in warm-blooded animals comprising administering to warm-blooded animals in need thereof an amount of a monoester of claim 1 sufficient to treat said tumors.
 17. The method of claim 16 wherein the Su(OH)₅ precursor is selected from the group consisting of D-mannose and xylitol. 